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RNU2-2

Chr 11ADAR

RNA, U2 small nuclear 2

Also known as: DEE119, RNU2-2P, RNU2B, U2

NCBI Gene: 26855 OMIM: 621238

This gene encodes the U2 small nuclear RNA, which is an essential component of the spliceosome that removes introns from pre-mRNA transcripts during RNA processing. Mutations cause developmental and epileptic encephalopathy 119, characterized by early-onset seizures and developmental delays affecting the central nervous system. The condition follows an autosomal dominant inheritance pattern.

OMIM ResearchSummary from OMIM

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 119MIM #621304

Clinical highlights

Gene–disease validity (ClinGen)

Strong · developmental and epileptic encephalopathy 119 · AD · ClinGen 2025

Interpreting a novel variant

Both loss of function mechanisms are described for this gene and which one applies is variant-dependent. Do not assume a null variant is — or isn't — the pathogenic class without checking the specific variant against curated evidence.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Splicing / LOF*

Mechanism· annotated

Some data sources returned errors (2)

ensembl: Error: Ensembl fetch failed: 400 for /lookup/symbol/homo_sapiens/RNU2-2?content-type=application/json

gnomad: Error: Gene not found

ReNU syndrome & the snRNA disorders — features, recurrent variants, where they sit, testing and counsellingOverview →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in RNU2-2?

gnomAD v4 · ~0k individuals · PASS only

Rare means allele frequency under

Rare missense

none observed

0 rare PASS variants

Rare truncating (LoF)

none observed

0 rare PASS variants

Rare synonymous (reference)

none observed

0 rare PASS variants

Rare missense and truncating variants are carried at similar rates in RNU2-2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Mechanism of Pathogenicity

Splicing / LOFvariant-dependent

Non-coding U2 spliceosomal snRNA (not a protein — gene-level protein-mechanism predictors do not apply). Heterozygous de novo variants (e.g. n.4, n.35) cause a dominant developmental and epileptic encephalopathy, thought to act by disrupting spliceosome function (aberrant splicing via altered U6/branch-site interactions) rather than haploinsufficiency. Separately, biallelic variants cause a clinically distinct — and notably prevalent — recessive disorder through loss of function: they destabilise the snRNA and reduce U2-2 expression by >90%. Mechanism is therefore variant- and zygosity-dependent.

References: PMID 40909831, PMID 40950445

Expert-curated annotation. Non-coding RNA gene — protein-based mechanism predictors (Badonyi & Marsh) do not apply.